We propose to investigate the kinetics and ultrastructure of megakaryocyte maturation under a number of experimental conditions: 1) humoral stimulation without concomittant alterations of circulating platelet levels; 2) during and after hypoxia, when production of red cells is respectively stimulated and suppressed; and 3)in in vitro culture systems. For in vivo analyses, megakaryocyte number, size, ploidy, and maturation rate will be measured and accompanying changes in platelet size and number will be determined. In all cases electron microscopy and cytochemistry will be used to elucidate the formation of specific subcellular organelles. The possibility of using immunocytochemical procedures to follow the genesis of megakaryocyte and platelet granules will be explored. Morphometric analysis of megakaryocytes and platelets will be done to determine qualitative differences in these cells under the above conditions. In addition, we will investigate the effect of altered host platelet levels in the behavior of transplanted pluripotential stem cells from different sources.